Rat CRM1 is responsible for the poor activity of human T-cell leukemia virus type 1 Rex protein in rat cells
Rat CRM1 is responsible for the poor activity of human T-cell leukemia virus type 1 Rex protein in rat cells
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DOI：
10.1128/jvi.75.23.11515-11525.2001
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发表时间：
2001-12-01
影响因子：
5.4
通讯作者：
Shida, H
中科院分区：
文献类型：
--
作者：
Hakata, Y;Yamada, M;Shida, H
人类 T 细胞白血病病毒 1 型 (HTLV-1) 相关疾病（如成人 T 细胞白血病和 HTLV-1 相关脊髓病/热带痉挛性截瘫）的大鼠模型已有报道。然而，这些模型并不能完全重现人类疾病，部分原因是 HTLV-1 在大鼠体内复制不佳。我们在这里调查了可能的原因。我们发现，与人类细胞相比，大鼠细胞中的 Rex 活性相当低。由于 Rex 功能很大程度上取决于 CRM1 蛋白，其人类类型（人类 CRM1 [hCRM1]）直接与 Rex 结合并将其从细胞核输出到细胞质，因此我们评估了大鼠 CRM1 (rCRM1) 是否可以像 hCRM1 一样作为 Rex 活性的辅助因子。我们首先克隆了编码 rCRM1 的 cDNA，发现 rCRM1 和 hCRM1 都能以相似的效率结合 Rex 蛋白并将其输出到细胞质。然而，与 hCRM1 不同，rCRM1 很难支持 Rex 功能，因为它诱导 RNA 输出到细胞质所需的 Rex-Rex 相互作用的能力较差。这些观察结果表明，rCRM1 作为 Rex 功能辅助因子的能力较差可能是 HTLV-1 在大鼠中复制不良的原因。
Rat models of human T-cell leukemia virus type 1 (HTLV-1)-related diseases such as adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis have been reported. However, these models do not completely reproduce human diseases partly because HTLV-1 replicates poorly in rats. We investigated here the possible reason for this. We found that the activity of Rex in rat cells is quite low compared to that in human cells. As Rex function depends largely on the CRM1 protein, whose human type (human CRM1 [hCRM1]) directly binds to Rex and exports it from the nucleus to the cytoplasm, we assessed whether rat CRM1 (rCRM1) could act as well as hCRM1 as a cofactor for Rex activity. We first cloned a cDNA encoding rCRM1 and found that both rCRM1 and hCRM1 could bind to and export Rex protein to the cytoplasm with similar efficiencies. However, unlike hCRM1, rCRM1 could hardly support Rex function because of its poor ability in inducing the Rex-Rex interaction required for RNA export into the cytoplasm. These observations suggest that the poor ability of rCRM1 to act as a cofactor for Rex function may be responsible for the poor replication of HTLV-1 in rats.